rs13222549

chr7-55157447-G-Cchr7-55157447-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):c.1208-216G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,236 control chromosomes in the GnomAD database, including 7,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7474 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18

Genes affected

EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-55157447-G-C is Benign according to our data. Variant chr7-55157447-G-C is described in ClinVar as [Benign]. Clinvar id is 1246809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.1208-216G>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.1208-216G>C		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46541 AN: 152118 Hom.: 7482 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46545 AN: 152236 Hom.: 7474 Cov.: 33 AF XY: 0.297 AC XY: 22100 AN XY: 74438

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.333

Alfa AF: 0.208 Hom.: 446

Bravo AF: 0.305

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.23
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13222549; hg19: chr7-55225140;